Cancer Research AACR Conference on Molecular Diagnostics - 2008 Translational Medicine Conference in Israel
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[Cancer Research 61, 4851-4857, June 15, 2001]
© 2001 American Association for Cancer Research

Tumor Biology

The Role of Thomsen-Friedenreich Antigen in Adhesion of Human Breast and Prostate Cancer Cells to the Endothelium1

Vladislav V. Glinsky, Gennadi V. Glinsky, Kate Rittenhouse-Olson, Margaret E. Huflejt, Olga V. Glinskii, Susan L. Deutscher and Thomas P. Quinn2

Department of Biochemistry, University of Missouri, Columbia, Missouri 65211 [V. V. G., O. V. G., S. L. D., T. P. Q.]; Cancer Research Center, Columbia, Missouri 65201 [V. V. G.]; Sidney Kimmel Cancer Center, San Diego, California 92121 [G. V. G., M. E. H.]; Metastat, Inc., San Diego, California 92121 [G. V. G.]; and Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, New York 14214 [K. R-O.]

Interactions of metastatic cancer cells with vasculatory endothelium are critical during early stages of cancer metastasis. Understanding the molecular underpinnings of these interactions is essential for the development of new efficacious cancer therapies. Here we demonstrate that cancer-associated carbohydrate T antigen plays a leading role in docking breast and prostate cancer cells onto endothelium by specifically interacting with endothelium-expressed ß-galactoside-binding protein, galectin-3. Importantly, T antigen-bearing glycoproteins are also capable of mobilizing galectin-3 to the surface of endothelial cells, thus priming them for harboring metastatic cancer cells. The T antigen-mediated, tumor-endothelial cell interactions could be efficiently disrupted using synthetic compounds either mimicking or masking this carbohydrate structure. High efficiency of T antigen-mimicking and T antigen-masking inhibitors of tumor cell adhesion warrants their further development into antiadhesive cancer therapeutics.




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Copyright © 2001 by the American Association for Cancer Research.